TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5000	15223;15224;15225	chr2:178734926;178734925;178734924	chr2:179599653;179599652;179599651
N2AB	4683	14272;14273;14274	chr2:178734926;178734925;178734924	chr2:179599653;179599652;179599651
N2A	3756	11491;11492;11493	chr2:178734926;178734925;178734924	chr2:179599653;179599652;179599651
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-33
• Domain position: 20
• Structural Position: 29
• Q(SASA): 0.4278
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/C	rs369933152	-0.201	0.999	N	0.613	0.392	None	gnomAD-2.1.1	1.13302E-04	None	None	None	None	N	None	1.17391E-03	2.89E-05	None	0	0	None	0	None	0	1.61E-05	0
R/C	rs369933152	-0.201	0.999	N	0.613	0.392	None	gnomAD-3.1.2	3.15424E-04	None	None	None	None	N	None	1.0376E-03	6.55E-05	0	0	0	None	0	0	2.94E-05	0	9.5511E-04
R/C	rs369933152	-0.201	0.999	N	0.613	0.392	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/C	rs369933152	-0.201	0.999	N	0.613	0.392	None	gnomAD-4.0.0	7.13735E-05	None	None	None	None	N	None	9.59795E-04	6.71727E-05	None	0	6.71892E-05	None	0	1.6518E-04	2.12146E-05	2.20138E-05	1.28263E-04
R/G	None	None	0.911	D	0.565	0.446	0.468003879618	gnomAD-4.0.0	6.85424E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16241E-05	0
R/H	rs377062348	-1.159	0.066	N	0.348	0.177	None	gnomAD-2.1.1	2.19E-05	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	3.31E-05	None	0	3.22E-05	0
R/H	rs377062348	-1.159	0.066	N	0.348	0.177	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	2.41E-05	2.61917E-04	0	0	0	None	0	0	4.41E-05	0	0
R/H	rs377062348	-1.159	0.066	N	0.348	0.177	None	gnomAD-4.0.0	2.42061E-05	None	None	None	None	N	None	2.67073E-05	8.39913E-05	None	0	4.47688E-05	None	1.56597E-05	0	1.44255E-05	1.21063E-04	1.6038E-05
R/P	None	None	0.986	D	0.617	0.422	0.317667799068	gnomAD-4.0.0	1.37079E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80109E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.4541	ambiguous	0.5099	ambiguous	-0.323	Destabilizing	0.525	D	0.567	neutral	None	None	None	None	N
R/C	0.1597	likely_benign	0.1686	benign	-0.319	Destabilizing	0.999	D	0.613	neutral	N	0.508574834	None	None	N
R/D	0.7553	likely_pathogenic	0.7972	pathogenic	0.08	Stabilizing	0.842	D	0.588	neutral	None	None	None	None	N
R/E	0.396	ambiguous	0.443	ambiguous	0.185	Stabilizing	0.842	D	0.619	neutral	None	None	None	None	N
R/F	0.5093	ambiguous	0.5453	ambiguous	-0.334	Destabilizing	0.974	D	0.617	neutral	None	None	None	None	N
R/G	0.3752	ambiguous	0.4335	ambiguous	-0.594	Destabilizing	0.911	D	0.565	neutral	D	0.601005943	None	None	N
R/H	0.0774	likely_benign	0.0775	benign	-1.078	Destabilizing	0.066	N	0.348	neutral	N	0.452814559	None	None	N
R/I	0.2753	likely_benign	0.3085	benign	0.382	Stabilizing	0.974	D	0.621	neutral	None	None	None	None	N
R/K	0.1162	likely_benign	0.1205	benign	-0.294	Destabilizing	0.688	D	0.627	neutral	None	None	None	None	N
R/L	0.2681	likely_benign	0.2893	benign	0.382	Stabilizing	0.911	D	0.563	neutral	N	0.449061247	None	None	N
R/M	0.3289	likely_benign	0.3649	ambiguous	-0.03	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
R/N	0.5701	likely_pathogenic	0.6036	pathogenic	0.097	Stabilizing	0.842	D	0.589	neutral	None	None	None	None	N
R/P	0.9072	likely_pathogenic	0.9234	pathogenic	0.169	Stabilizing	0.986	D	0.617	neutral	D	0.601005943	None	None	N
R/Q	0.0921	likely_benign	0.1027	benign	-0.027	Destabilizing	0.949	D	0.649	neutral	None	None	None	None	N
R/S	0.4419	ambiguous	0.4881	ambiguous	-0.487	Destabilizing	0.285	N	0.431	neutral	N	0.445284459	None	None	N
R/T	0.2427	likely_benign	0.2691	benign	-0.211	Destabilizing	0.728	D	0.559	neutral	None	None	None	None	N
R/V	0.3241	likely_benign	0.3548	ambiguous	0.169	Stabilizing	0.974	D	0.597	neutral	None	None	None	None	N
R/W	0.1986	likely_benign	0.2148	benign	-0.187	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	N
R/Y	0.3562	ambiguous	0.3785	ambiguous	0.174	Stabilizing	0.949	D	0.617	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.